Potential physiological, anthropometric, and training determinants of running economy (RE) were studied in a heterogeneous group of habitual distance runners (N = 188, 119 males, 69 females). RE was measured as VO2 (ml.kg-1.min-1) during level treadmill running at 161 m.min-1 (6 mph) (VO2-6). Examined as potential determinants of RE were heart rate and ventilation while running at 6 mph (HR6, VE6), VO2max (ml.kg-1 x min-1), % fat, age, gender, height, weight, estimated leg mass, typical training pace, training volume, and sit-and-reach test performance. RE was entered as the dependent variable and the potential determinants as independent variables in zero-order correlation and multiple regression analyses. Zero-order correlation analysis found VO2max, HR6, and VE6 to be significantly, positively correlated with VO2-6 (P < 0.001). Multiple regression analysis, in which the independent effect of each predictor variable was examined, revealed VO2-6 to be positively correlated with VO2max (P < 0.001), HR6 (P < 0.001), VE6 (P < 0.001), and age (P < 0.05) and negatively correlated with weight (P < 0.01). These findings indicate that, in a diverse group of runners, better RE (VO2-6) is associated with lower VO2max, lower submaximal exercise VE and HR, lower age, and greater weight.